Under Construction: Genome Remodeling Makes Group A Streptococcus More Virulent

Streptococcus pyogenes, also known as group A streptococcus (GAS), is a gram positive bacterium best known for causing pharyngitis ("strep throat"). In some cases, however, GAS causes more severe diseases such as glomerulonephritis, acute rheumatic fever, and even necrotizing fasciitis (the ever provocative "flesh eating" bacteria).

Recently, one strain of GAS, termed emm89, has proven itself particularly successful at infecting patients across the UK and Canada. Between 1998 and 2009, clinicians at Imperial College Healthcare NHS Trust in London noticed an increase in infections caused by emm89. Curiously, this strain is not antibiotic resistant, suggesting some other mechanism by which emm89 causes invasive disease.

Researchers at Imperial College London wanted to know if specific genetic changes in emm89 contributed to its increased virulence. To answer this question, Junior Research Fellow Claire Turner and colleagues sequenced the genomes of both invasive and non-invasive emm89 isolates. They report their findings in the most recent issue of the journal mBio.

The group sequenced the genomes of emm89 samples isolated from patients between 2004 and 2013. They identified six regions in which homologous recombination had occurred when compared to a particularly virulent emm89 strain (that caused necrotizing fasciitis). The most surprising change in these invasive emm89 strains was that they lacked a capsule, the outermost layer of the cell. "The fact that it had lost its capsule was a complete surprise", says Turner, "because it was believed that the capsule was essential for group A streptococcus to cause invasive disease". Cells lacking capsule tend to stick to surfaces better, which could be one reason emm89 is more successful at infecting humans.

The invasive emm89 isolates also produced more streptolysin O and NAD(+)-glycohydrolase (NADase). Streptolysin O creates pores in host cells through which NADase enters, eventually resulting in cell death.

These findings should motivate healthcare professionals to assess the selective pressures we place on the microbes around us. According to Shiranee Sriiskanda, lead investigator of the study, "We know very little about how group A streptococcus is transmitted from person to person. We need to look into this more deeply and think about better ways to prevent transmission".

Sources: mBio ("Emergence of a New Highly Successful Acapsular Group A Streptococcus Clade of Genotype emm89 in the United Kingdom" DOI:10.1128/mBio.00622-15), Science Daily, CDC